The Role of Interferon for the Treatment of Chronic Hepatitis C Virus Infection

  • Saleh A. Alqahtani
  • Mark S. SulkowskiEmail author
Part of the Topics in Medicinal Chemistry book series (TMC, volume 31)


For many years the only available therapy for chronic hepatitis C virus (HCV) infection was interferon-based therapy. Interferons are a family of cytokines that are an essential part of the body’s natural response to viral pathogens. In 1991, interferon-α (IFN-α) injections were first approved by the Food and Drug Administration for the treatment of HCV infection and remained the backbone of therapy until late 2014. As monotherapy, IFN-α injected thrice weekly yielded low sustained virologic response (SVR) rates. In 1998, the addition of ribavirin, a broad-spectrum, non-specific antiviral agent, decreased liver inflammation alone and, in combination with IFN-α, increased the SVR rate; however, the addition of ribavirin also increased side effects. In the early 2000s, IFN-α plus ribavirin combination treatment was further improved by the development of longer-acting pegylated IFN-α (PegIFN-α). While this reduced the need for subcutaneous injections from three times a week to once a week which improved patients’ adherence, the increase in SVR with PegIFN-α over standard IFN-α was relatively modest. Further, drug-related side effects remained problematic, limiting HCV treatment uptake and effectiveness. In the early direct-acting antiviral (DAA) era, PegIFN-α and ribavirin were used in combination with DAAs to prevent drug resistance and increase the SVR rate. With the advent of combination DAA regimens, the role of IFN-α decreased dramatically and, in late 2017, IFN-α was no longer recommended by professional societies as a first-line treatment for any HCV genotype or patient population, marking the end of the IFN-α era.


Chronic infection Hepatitis C virus Inflammation Interferon Therapy 


Compliance with Ethical Standards

Conflict of Interest Author declares that he has no conflict of interest.

Ethical Approval Not applicable.


  1. 1.
    Nayak A, Pattabiraman N, Fadra N, Goldman R, Kosakovsky Pond SL, Mazumder R (2015) Structure-function analysis of hepatitis C virus envelope glycoproteins E1 and E2. J Biomol Struct Dyn 33(8):1682–1694PubMedGoogle Scholar
  2. 2.
    Parekh PJ, Shiffman ML (2014) The role of interferon in the new era of hepatitis C treatments. Expert Rev Gastroenterol Hepatol 8(6):649–656PubMedGoogle Scholar
  3. 3.
    Lin FC, Young HA (2014) Interferons: Success in anti-viral immunotherapy. Cytokine Growth Factor Rev 25(4):369–376PubMedPubMedCentralGoogle Scholar
  4. 4.
    Muir AJ, Shiffman ML, Zaman A, Yoffe B, de la Torre A, Flamm S et al (2010) Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 52(3):822–832PubMedGoogle Scholar
  5. 5.
    Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Di Bisceglie A, Peters M et al (1986) Treatment of chronic non-A,non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med 315(25):1575–1578PubMedGoogle Scholar
  6. 6.
    Lai MY, Kao JH, Yang PM, Wang JT, Chen PJ, Chan KW et al (1996) Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Gastroenterology 111(5):1307–1312PubMedGoogle Scholar
  7. 7.
    Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E et al (2000) Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med 343(23):1666–1672Google Scholar
  8. 8.
    Ishikawa T, Kubota T, Abe H, Nagashima A, Hirose K, Togashi T et al (2012) Efficacy of the regimen using twice-daily beta-interferon followed by the standard of care for chronic hepatitis C genotype 1b with high viral load. Hepatol Res 42(9):864–869PubMedGoogle Scholar
  9. 9.
    Liu C, Zhu H, Subramanian GM, Moore PA, Xu Y, Nelson DR (2007) Anti-hepatitis C virus activity of albinterferon alfa-2b in cell culture. Hepatol Res 37(11):941–947PubMedGoogle Scholar
  10. 10.
    Blatt LM, Davis JM, Klein SB, Taylor MW (1996) The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon. J Interf Cytokine Res 16(7):489–499Google Scholar
  11. 11.
    Ghosh D, Ghosh D, Parida P (2016) Physiological proteins in therapeutics: a current review on interferons. Mini Rev Med Chem 16(12):947–952PubMedGoogle Scholar
  12. 12.
    Carlson RJ, Doucette JR, Knox K, Nazarali AJ (2015) Pharmacogenomics of interferon-beta in multiple sclerosis: what has been accomplished and how can we ensure future progress? Cytokine Growth Factor Rev 26(2):249–261PubMedGoogle Scholar
  13. 13.
    Yoshida J, Mizuno M, Wakabayashi T (2004) Interferon-beta gene therapy for cancer: basic research to clinical application. Cancer Sci 95(11):858–865PubMedGoogle Scholar
  14. 14.
    Razaghi A, Owens L, Heimann K (2016) Review of the recombinant human interferon gamma as an immunotherapeutic: impacts of production platforms and glycosylation. J Biotechnol 240:48–60PubMedGoogle Scholar
  15. 15.
    van Pesch V, Lanaya H, Renauld JC, Michiels T (2004) Characterization of the murine alpha interferon gene family. J Virol 78(15):8219–8228PubMedPubMedCentralGoogle Scholar
  16. 16.
    Gibbert K, Schlaak JF, Yang D, Dittmer U (2013) IFN-alpha subtypes: distinct biological activities in anti-viral therapy. Br J Pharmacol 168(5):1048–1058PubMedPubMedCentralGoogle Scholar
  17. 17.
    Jaks E, Gavutis M, Uze G, Martal J, Piehler J (2007) Differential receptor subunit affinities of type I interferons govern differential signal activation. J Mol Biol 366(2):525–539PubMedGoogle Scholar
  18. 18.
    Sato I, Shimbo T, Kawasaki Y, Masaki N (2015) Comparison of peginterferon alfa-2a and alfa-2b for treatment of patients with chronic hepatitis C: a retrospective study using the Japanese Interferon Database. Drug Des Devel Ther 9:283–290PubMedGoogle Scholar
  19. 19.
    Chen J, Florian J, Carter W, Fleischer RD, Hammerstrom TS, Jadhav PR et al (2013) Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies. Gastroenterology 144(7):1450–1455.e2PubMedGoogle Scholar
  20. 20.
    Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244(4902):359–362Google Scholar
  21. 21.
    National Institutes of Health (2002) National Institutes of Health Consensus Development Conference Statement: Management of hepatitis C: 2002 – June 10–12, 2002. Hepatology 36(5 Suppl 1):S3–S20Google Scholar
  22. 22.
    Liu Z, Que S, Xu J, Peng T (2014) Alanine aminotransferase-old biomarker and new concept: a review. Int J Med Sci 11(9):925–935PubMedPubMedCentralGoogle Scholar
  23. 23.
    Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC Jr, Perrillo RP et al (1989) Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. N Engl J Med 321(22):1501–1506PubMedGoogle Scholar
  24. 24.
    Di Bisceglie AM, Martin P, Kassianides C, Lisker-Melman M, Murray L, Waggoner J et al (1989) Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N Engl J Med 321(22):1506–1510PubMedGoogle Scholar
  25. 25.
    Poynard T, Leroy V, Cohard M, Thevenot T, Mathurin P, Opolon P et al (1996) Meta-analysis of interferon randomized trials in the treatment of viral hepatitis C: effects of dose and duration. Hepatology 24(4):778–789PubMedGoogle Scholar
  26. 26.
    Lau DT, Kleiner DE, Ghany MG, Park Y, Schmid P, Hoofnagle JH (1998) 10-Year follow-up after interferon-alpha therapy for chronic hepatitis C. Hepatology 28(4):1121–1127PubMedGoogle Scholar
  27. 27.
    Sleijfer S, Bannink M, Van Gool AR, Kruit WH, Stoter G (2005) Side effects of interferon-alpha therapy. Pharm World Sci 27(6):423–431PubMedGoogle Scholar
  28. 28.
    Wu LS, Rower JE, Burton JR Jr, Anderson PL, Hammond KP, Baouchi-Mokrane F et al (2015) Population pharmacokinetic modeling of plasma and intracellular ribavirin concentrations in patients with chronic hepatitis C virus infection. Antimicrob Agents Chemother 59(4):2179–2188PubMedPubMedCentralGoogle Scholar
  29. 29.
    Bodenheimer HC Jr, Lindsay KL, Davis GL, Lewis JH, Thung SN, Seeff LB (1997) Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial. Hepatology 26(2):473–477PubMedGoogle Scholar
  30. 30.
    Brok J, Gluud LL, Gluud C (2009) Ribavirin monotherapy for chronic hepatitis C. Cochrane Database Syst Rev 4:CD005527Google Scholar
  31. 31.
    Tong MJ, Hwang SJ, Lefkowitz M, Lee SD, Co RL, Conrad A et al (1994) Correlation of serum HCV RNA and alanine aminotransferase levels in chronic hepatitis C patients during treatment with ribavirin. J Gastroenterol Hepatol 9(6):587–591PubMedGoogle Scholar
  32. 32.
    Reichard O, Norkrans G, Fryden A, Braconier JH, Sonnerborg A, Weiland O (1998) Randomised, double-blind, placebo-controlled trial of interferon alpha-2b with and without ribavirin for chronic hepatitis C. The Swedish Study Group. Lancet 351(9096):83–87PubMedGoogle Scholar
  33. 33.
    Schalm SW, Hansen BE, Chemello L, Bellobuono A, Brouwer JT, Weiland O et al (1997) Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C. Meta-analysis of individual patient data from European centers. J Hepatol 26(5):961–966PubMedGoogle Scholar
  34. 34.
    McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK et al (1998) Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 339(21):1485–1492PubMedGoogle Scholar
  35. 35.
    Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G et al (1998) Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet 352(9138):1426–1432PubMedGoogle Scholar
  36. 36.
    Rotman Y, Noureddin M, Feld JJ, Guedj J, Witthaus M, Han H et al (2014) Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C. Gut 63(1):161–169PubMedGoogle Scholar
  37. 37.
    McHutchison JG, Poynard T (1999) Combination therapy with interferon plus ribavirin for the initial treatment of chronic hepatitis C. Semin Liver Dis 19(Suppl 1):57–65PubMedGoogle Scholar
  38. 38.
    Sulkowski MS, Cooper C, Hunyady B, Jia J, Ogurtsov P, Peck-Radosavljevic M et al (2011) Management of adverse effects of Peg-IFN and ribavirin therapy for hepatitis C. Nat Rev Gastroenterol Hepatol 8(4):212–223PubMedGoogle Scholar
  39. 39.
    Soota K, Maliakkal B (2014) Ribavirin induced hemolysis: a novel mechanism of action against chronic hepatitis C virus infection. World J Gastroenterol 20(43):16184–16190PubMedPubMedCentralGoogle Scholar
  40. 40.
    Wu JZ, Larson G, Walker H, Shim JH, Hong Z (2005) Phosphorylation of ribavirin and viramidine by adenosine kinase and cytosolic 5′-nucleotidase II: implications for ribavirin metabolism in erythrocytes. Antimicrob Agents Chemother 49(6):2164–2171PubMedPubMedCentralGoogle Scholar
  41. 41.
    Page T, Connor JD (1990) The metabolism of ribavirin in erythrocytes and nucleated cells. Int J Biochem 22(4):379–383PubMedGoogle Scholar
  42. 42.
    De Franceschi L, Fattovich G, Turrini F, Ayi K, Brugnara C, Manzato F et al (2000) Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: role of membrane oxidative damage. Hepatology 31(4):997–1004PubMedGoogle Scholar
  43. 43.
    (1999) EASL International Consensus Conference on hepatitis C. Paris, 26–27 February 1999. Consensus statement. J Hepatol 31(Suppl 1):3–8Google Scholar
  44. 44.
    Glue P, Fang JW, Rouzier-Panis R, Raffanel C, Sabo R, Gupta SK et al (2000) Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group. Clin Pharmacol Ther 68(5):556–567PubMedGoogle Scholar
  45. 45.
    Baker DE (2001) Pegylated interferons. Rev Gastroenterol Disord 1(2):87–99PubMedGoogle Scholar
  46. 46.
    Zeuzem S, Welsch C, Herrmann E (2003) Pharmacokinetics of peginterferons. Semin Liver Dis 23(Suppl 1):23–28PubMedGoogle Scholar
  47. 47.
    Reddy KR, Wright TL, Pockros PJ, Shiffman M, Everson G, Reindollar R et al (2001) Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C. Hepatology 33(2):433–438PubMedGoogle Scholar
  48. 48.
    Lindsay KL, Trepo C, Heintges T, Shiffman ML, Gordon SC, Hoefs JC et al (2001) A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology 34(2):395–403PubMedGoogle Scholar
  49. 49.
    Heathcote EJ, Shiffman ML, Cooksley WG, Dusheiko GM, Lee SS, Balart L et al (2000) Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med 343(23):1673–1680PubMedGoogle Scholar
  50. 50.
    Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr et al (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347(13):975–982PubMedPubMedCentralGoogle Scholar
  51. 51.
    Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P et al (2004) Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140(5):346–355PubMedGoogle Scholar
  52. 52.
    Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R et al (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358(9286):958–965Google Scholar
  53. 53.
    McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J et al (2009) Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 361(6):580–593PubMedGoogle Scholar
  54. 54.
    Rumi MG, Aghemo A, Prati GM, D’Ambrosio R, Donato MF, Soffredini R et al (2010) Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plus ribavirin in chronic hepatitis C. Gastroenterology 138(1):108–115PubMedGoogle Scholar
  55. 55.
    Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG et al (2010) Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection. Gastroenterology 138(1):116–122PubMedGoogle Scholar
  56. 56.
    Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ et al (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461(7262):399–401PubMedGoogle Scholar
  57. 57.
    Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV et al (2010) Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 139(1):120–9.e18PubMedGoogle Scholar
  58. 58.
    Rosen HR (2011) Clinical practice. Chronic hepatitis C infection. N Engl J Med 364(25):2429–2438PubMedGoogle Scholar
  59. 59.
    Moreno C, Deltenre P, Pawlotsky JM, Henrion J, Adler M, Mathurin P (2010) Shortened treatment duration in treatment-naive genotype 1 HCV patients with rapid virological response: a meta-analysis. J Hepatol 52(1):25–31PubMedGoogle Scholar
  60. 60.
    Ahn SH, Lee HW, Kim YS, Kim JK, Han KH, Chon CY et al (2009) Recombinant interferon-Beta-1alpha plus ribavirin for the treatment of chronic HCV infection: a prospective, randomized, comparative pilot study. Gut Liver 3(1):20–25PubMedPubMedCentralGoogle Scholar
  61. 61.
    Inoue K, Watanabe T, Yamada M, Yoshikumi H, Ogawa O, Yoshiba M (2009) Efficacy of interferon Beta combined with cyclosporine induction and intensified therapy for retreatment of chronic hepatitis C. Transplant Proc 41(1):246–249PubMedGoogle Scholar
  62. 62.
    Pellicano R, Craxi A, Almasio PL, Valenza M, Venezia G, Alberti A et al (2005) Interferon beta-1a alone or in combination with ribavirin: a randomized trial to compare efficacy and safety in chronic hepatitis C. World J Gastroenterol 11(29):4484–4489PubMedPubMedCentralGoogle Scholar
  63. 63.
    Sasaki R, Kanda T, Nakamoto S, Haga Y, Nakamura M, Yasui S et al (2015) Natural interferon-beta treatment for patients with chronic hepatitis C in Japan. World J Hepatol 7(8):1125–1132PubMedPubMedCentralGoogle Scholar
  64. 64.
    Matsuda F, Torii Y, Enomoto H, Kuga C, Aizawa N, Iwata Y et al (2012) Anti-interferon-alpha neutralizing antibody is associated with nonresponse to pegylated interferon-alpha plus ribavirin in chronic hepatitis C. J Viral Hepat 19(10):694–703PubMedGoogle Scholar
  65. 65.
    Ramos EL (2010) Preclinical and clinical development of pegylated interferon-lambda 1 in chronic hepatitis C. J Interf Cytokine Res 30(8):591–595Google Scholar
  66. 66.
    Donnelly RP, Dickensheets H, O’Brien TR (2011) Interferon-lambda and therapy for chronic hepatitis C virus infection. Trends Immunol 32(9):443–450PubMedPubMedCentralGoogle Scholar
  67. 67.
    Elazar M, Glenn JS (2017) Emerging concepts for the treatment of hepatitis delta. Curr Opin Virol 24:55–59PubMedGoogle Scholar
  68. 68.
    Osborn BL, Olsen HS, Nardelli B, Murray JH, Zhou JX, Garcia A et al (2002) Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 303(2):540–548PubMedGoogle Scholar
  69. 69.
    Nelson DR, Benhamou Y, Chuang WL, Lawitz EJ, Rodriguez-Torres M, Flisiak R et al (2010) Albinterferon Alfa-2b was not inferior to pegylated interferon-alpha in a randomized trial of patients with chronic hepatitis C virus genotype 2 or 3. Gastroenterology 139(4):1267–1276PubMedPubMedCentralGoogle Scholar
  70. 70.
    Zeuzem S, Sulkowski MS, Lawitz EJ, Rustgi VK, Rodriguez-Torres M, Bacon BR et al (2010) Albinterferon Alfa-2b was not inferior to pegylated interferon-alpha in a randomized trial of patients with chronic hepatitis C virus genotype 1. Gastroenterology 139(4):1257–1266PubMedGoogle Scholar
  71. 71.
    Fattovich G, Zagni I, Minola E, Felder M, Rovere P, Carlotto A et al (2003) A randomized trial of consensus interferon in combination with ribavirin as initial treatment for chronic hepatitis C. J Hepatol 39(5):843–849PubMedGoogle Scholar
  72. 72.
    Bacon BR, Shiffman ML, Mendes F, Ghalib R, Hassanein T, Morelli G et al (2009) Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results. Hepatology 49(6):1838–1846PubMedGoogle Scholar
  73. 73.
    Nordstrom EM, Biggins SW, Gralla J, Rosen HR, Everson GT, Burton JR Jr (2015) Consensus interferon for recurrent hepatitis C infection in nonresponders to peginterferon and ribavirin after liver transplant. Exp Clin Transplant 13(6):543–549PubMedGoogle Scholar
  74. 74.
    Soriano V, Vispo E, Poveda E, Labarga P, Martin-Carbonero L, Fernandez-Montero JV et al (2011) Directly acting antivirals against hepatitis C virus. J Antimicrob Chemother 66(8):1673–1686PubMedGoogle Scholar
  75. 75.
    Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH et al (2011) Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 364(25):2405–2416PubMedPubMedCentralGoogle Scholar
  76. 76.
    Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS et al (2011) Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 364(13):1195–1206PubMedPubMedCentralGoogle Scholar
  77. 77.
    Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, Everson GT et al (2011) Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med 365(11):1014–1024Google Scholar
  78. 78.
    Jacobson IM, Pawlotsky JM, Afdhal NH, Dusheiko GM, Forns X, Jensen DM et al (2012) A practical guide for the use of boceprevir and telaprevir for the treatment of hepatitis C. J Viral Hepat 19(Suppl 2):1–26PubMedGoogle Scholar
  79. 79.
    Poordad F, Bronowicki JP, Gordon SC, Zeuzem S, Jacobson IM, Sulkowski MS et al (2012) Factors that predict response of patients with hepatitis C virus infection to boceprevir. Gastroenterology 143(3):608–618 e5PubMedGoogle Scholar
  80. 80.
    Lawitz E, Lalezari JP, Hassanein T, Kowdley KV, Poordad FF, Sheikh AM et al (2013) Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis 13(5):401–408PubMedGoogle Scholar
  81. 81.
    Gutierrez JA, Lawitz EJ, Poordad F (2015) Interferon-free, direct-acting antiviral therapy for chronic hepatitis C. J Viral Hepat 22(11):861–870PubMedGoogle Scholar
  82. 82.
    de Leuw P, Stephan C (2018) Protease inhibitor therapy for hepatitis C virus-infection. Expert Opin Pharmacother 19(6):577–587PubMedGoogle Scholar
  83. 83.
    AASLD-IDSA HCV Guidance Panel (2018) Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis 67(10):1477–1492Google Scholar
  84. 84.
    Gane E, Lawitz E, Pugatch D, Papatheodoridis G, Brau N, Brown A et al (2017) Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment. N Engl J Med 377(15):1448–1455PubMedGoogle Scholar

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© Springer Nature Switzerland AG  2019

Authors and Affiliations

  1. 1.Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of MedicineViral Hepatitis Center, The Johns Hopkins HospitalBaltimoreUSA

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